a phase 2 study of asonep™ to treat unresectable and refractory renal cell carcinoma

Conditions: Renal Cell Carcinoma

Summary: this phase 2a study will investigate the efficacy, safety and tolerability of asonep™ (sonepcizumab/lt1009) when administered intravenously once a week, every 4 weeks (or cycle), to subjects with refractory renal cell carcinoma (rcc) until the disease progresses. subjects who have failed 3 prior treatments for rcc including vascular endothelial growth factor (vegf) and/or mammalian target of rapamycin (mtor) inhibitors or who have tumors that cannot be surgically removed will be eligible for screening.

lt1009-onc-002 is a phase 2a open-label, multi-center study designed to evaluate the efficacy and safety of asonep (sonepcizumab/lt1009) monotherapy in subjects with advanced, unresectable, refractory rcc who have previously failed up to 3 therapies, including vegf and/or mtor inhibitors. two cohorts will be enrolled for a total of up to 39 subjects. subjects will receive an intravenous (iv) infusion of asonep™ over 90 minutes at 24 mg/kg once a week and progression-free survival (pfs) will be assessed after 8 weeks of treatment. cohort 1 will enroll approximately 22 subjects. a second cohort of up to 17 subjects will be enrolled if at least 12 out of 22 subjects from cohort 1 demonstrated pfs at 8 weeks. weekly dosing will take place from the date of randomization until the date of first documented progression or date of death from any cause, whichever comes first.

Eligibility criteria:
inclusion criteria: * unresectable, locally advanced recurrent or metastatic rcc * histological or cytological confirmation of clear cell rcc - core tissue biopsy of either primary tumor or metastatic lesion with paraffin-embedded tissue specimens if no prior nephrectomy * measurable disease by recist 1.1 * had one prior therapy for unresectable rcc with a vegf/vegfr targeted therapy (sunitinib, sorafenib, other vegfr tki or bevacizumab) - one prior treatment with an mtor inhibitor (everolimus, temsirolimus or sirolimus) for unresectable disease permitted-prior immunotherapy (immunomodulators such as cytokines, interleukins, vaccines, etc.) such as il-2 also permitted * male or non-pregnant, non-nursing female * life expectancy ≥3 months * ecog performance status of 0, 1 or 2 * must not be receiving any concurrent anticancer therapy * baseline ct or mri scans of measurable disease sites by recist 1.1 performed within 2 weeks of day 0 - for subjects with bone metastases, baseline bone scan performed within 4 weeks of study entry * adequate organ and immune function (within 7 days of day 0): hemoglobin \>9 g/dl-absolute neutrophil count \>1500 cells/ul without growth factors-platelet count ≥100x10\^9/l without transfusion-serum creatinine \ 40 ml/min-total bilirubin \<1.5x uln-ast/alt \<2.5x uln (or \<5.0x uln if liver metastases present)-inr and aptt \<1.5x uln * subject lesions for arterial spin labeling (asl) mri ≥2.5cm by ct imaging * must understand, be able and willing to fully comply with study procedures exclusion criteria: * prior treatment with \>3 vegf pathway and/or mtor inhibitors for rc cancer * history of other cns disease (spinal cord compression, or evidence of symptomatic brain or leptomeningeal carcinomatosis) * major surgery within 4 weeks of day 0 * radiation therapy within 4 weeks of baseline/infusion. prior palliative radiation to metastatic lesions is acceptable if there is at least one measurable, non-radiated lesion * uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on day 0 * known or suspected intolerance or hypersensitivity to study materials or any excipients * evidence of bowel obstruction because of theoretical possibility of gi perforation with an anti-angiogenesis agent * severe hemorrhage within 4 weeks of screening * history of gi perforation * history of non-healing wounds including ulcer or delayed bone fractures * prolonged qtc interval on baseline ecg (\>450 msec for males or \>470 msec for females), cardiac dysrhythmias including atrial fibrillation, torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (\<60 bpm), heart block (excluding 1st degree block, being pr interval prolongation only), congenital long qt syndrome or new st segment elevation or depression or new q wave on ecg * secondary malignancy within the last 5 years, except for adequately-treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer * previously enrolled in an sonepcizumab study or into this study and subsequently withdrawn * history of alcohol or other substance abuse within the last year * use of corticosteroids or other immunosuppression (if taking systemic steroids \[vs. topical\], at least 4 weeks must have passed since the last dose) * growth factors within 1 week of screening * serious medical conditions that might be aggravated by treatment or limit compliance * cerebrovascular accident or transient ischemic attack, or pulmonary embolism within 6 months prior to screening * participation in another clinical trial * other severe or intercurrent acute or chronic medical or psychiatric condition or laboratory abnormality that may increase risk associated with study participation or study drug administration

Keywords: renal cell carcinoma renal cell cancer asonep sonepcizumab